Development of a Bilayer Tablet by Fused Deposition Modeling as a Sustained-Release Drug Delivery System.

Three-dimensional printing by fused deposition modeling (FDM) coupled with hot-melt extrusion (HME) is a point of convergence of research efforts directed toward the development of personalized dosage forms. In addition to the customization in terms of shapes, sizes, or delivered drug doses, the modulation of drug release profiles is crucial to ensure the superior efficacy and safety of modern 3D-printed medications compared to those of conventional ones. Our work aims to solidify the groundwork for the preparation of 3D-printed tablets that ensure the sustained release of diclofenac sodium. Specifically, we achieved the fast release of a diclofenac sodium dose to allow for the prompt onset of its pharmacological effect, further sustaining by the slow release of another dose to maintain the effect over a prolonged timeframe. In this regard, proper formulation and design strategies (a honeycomb structure for the immediate-release layer and a completely filled structure for the sustained-release layer) were applied. Secondarily, the potential of polyvinyl alcohol to function as a multifaceted polymeric matrix for both the immediate and slow-release layers was explored, with the objective of promoting the real-life applicability of the technique by downsizing the number of materials required to obtain versatile pharmaceutical products. The present study is a step forward in the translation of HME-FDM-3DP into a pharmaceutical manufacturing methodology.

QbD guided development of immediate release FDM-3D printed tablets with customizable API doses.

The objective of this work was to develop a fused deposition modeling (FDM) 3D printed immediate release (IR) tablet with flexibility in adjusting the dose of the active pharmaceutical ingredient (API) by scaling the size of the dosage form and appropriate drug release profile steadiness to the variation of dimensions or thickness of the deposited layers throughout the printing process. Polyvinyl alcohol-based filaments with elevated API content (50% w/w) were prepared by hot melt extrusion (HME), through systematic screening of polymeric formulations with different drug loadings, and their printability was evaluated by means of mechanical characterization. For the tablet fabrication step by 3D printing (3DP), the Quality by Design (QbD) approach was implemented by employing risk management strategies and Design of Experiments (DoE). The effects of the tablet design, tablet size and the layer height settings on the drug release and the API content were investigated. Between the two proposed original tablet architectures, the honeycomb configuration was found to be a suitable candidate for the preparation of IR dosage forms with readily customizable API doses. Also, a predictive model was obtained, which assists the optimization of variables involved in the printing phase and thereby facilitates the tailoring process.

Polyvinyl Alcohol-Based 3D Printed Tablets: Novel Insight into the Influence of Polymer Particle Size on Filament Preparation and Drug Release Performance.

Three-dimensional printing (3DP) by fused deposition modeling (FDM) has gained momentum as a promising pharmaceutical manufacturing method due to encouraging forward-looking perspectives in personalized medicine preparation. The current challenges the technology has for applicability in the fabrication of solid dosage forms include the limited range of suitable pharmaceutical grade thermoplastic materials. Hence, it is important to investigate the implications of variable properties of the polymeric carrier on the preparation steps and the final output, as versatile products could be obtained by using the same material. In this study, we highlighted the influence of polyvinyl alcohol (PVA) particle size on the residence time of the mixtures in the extruder during the drug-loaded filament preparation step and the consequent impact on drug release from the 3D printed dosage form. We enhanced filament printability by exploiting the plasticizing potential of the active pharmaceutical ingredient (API) and we explored a channeled tablet model as a design strategy for dissolution facilitating purposes. Our findings disclosed a new perspective regarding material considerations for the preparation of PVA-based solid dosage forms by coupling hot melt extrusion (HME) and FDM-3DP.

Antispasmodic Effect of Essential Oils and Their Constituents: A Review.

The antispasmodic effect of drugs is used for the symptomatic treatment of cramping and discomfort affecting smooth muscles from the gastrointestinal, billiary or genitourinary tract in a variety of clinical situations.The existing synthetic antispasmodic drugs may cause a series of unpleasant side effects, and therefore the discovery of new molecules of natural origin is an important goal for the pharmaceutical industry. This review describes a series of recent studies investigating the antispasmodic effect of essential oils from 39 plant species belonging to 12 families. The pharmacological models used in the studies together with the mechanistic discussions and the chemical composition of the essential oils are also detailed. The data clearly demonstrate the antispasmodic effect of the essential oils from the aromatic plant species studied. Further research is needed in order to ascertain the therapeutic importance of these findings.

Concepts and Challenges of Biosimilars in Breast Cancer: The Emergence of Trastuzumab Biosimilars.

With the development of anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibodies, trastuzumab-based therapy has become the standard of care among patients with early or advanced HER2-positive breast cancer. However, real-world data have shown that up to a half of patients do not receive trastuzumab or any other HER2-targeted agent, mainly due to high treatments costs. The prospect of a more enlarged access to trastuzumab treatment lies in the use of biosimilars, as the European and the US patent of the reference products has or will soon expire. Biosimilars are biologics highly similar in terms of quality characteristics, biological activity, safety and efficacy to already approved biologics. The biosimilarity of any European Union (EU)-approved biosimilar is guaranteed based on the comprehensive comparability exercise which includes comparative analytical, non-clinical and clinical studies. In the matter of biosimilars' interchangeability and substitution, the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) have adopted different positions, triggering various discussions on the potential immunogenicity and efficacy in individual patients. As more biosimilars are gaining approval, the present review aims to offer concise information for oncologists and pharmacists about the production, approval, interchangeability, and substitution policies of biosimilars used in breast cancer therapy, with a special focus on trastuzumab.